Melanocyte protein PMEL17 is an integral membrane protein that undergoes export from the endoplasmic reticulum to the Golgi apparatus where it is glycosylated and ultimately trafficked to the melanosome. The specific route by which mature PMEL17 makes it way to the melanosome has been a subject of debate, however, it is apparent that some fraction of the protein is presented transiently at the cell surface prior to its entry into stage I melanosomes. Melanosomes are a specialized lysosome-related organelle that produce melanin pigments, which are deposited on fibrils composed of proteolytic fragments derived from the PMEL17 protein. The synthesis of melanin pigments is largely restricted to melanocytes and the post-mitotic pigment epithelium of the eye. Melanocytes uniquely express specialized genes required for pigment formation, some of which are maintained following their transformation to melanoma.
Human PMEL17 is a 661 amino acid protein (including the amino-terminal signal sequence), with a transmembrane region located at amino acids 596 and 616. PMEL17 undergoes complex processing, but at least a portion of the protein's lifecycle is spent on the cell surface.
There is a need in the art for agents that target PMEL17 for the diagnosis and treatment of PMEL17-associated conditions, such as cancer. The invention fulfills that need and provides other benefits.